Diabetic Nephropathy is the leading cause of end-stage-renal disease in the US. It is essential to identify new pathways that are important in the pathogenesis of this disease. Glomerular volume, fibrosis and open giomerutar capillary loops will be evaluated by in kidneys of diabetic (db/db) and non-diabetic (dbZm) mice with multi-photon laser scanning microscope (MPLSM), Reference will be established for all these parameters and will be correlated to conventional measurements. In vivo observed phenotypic changes of diabetic glomerular disease will be correlated with molecular patterns of gene expression. By removing single glomeruli with known phenotypic appearance from live animals. This project is intended to a) establish a new technology to describe phenotypic changes in diabetic renal disease b) provide a new method for tissue sampling and gene expression monitoring c) translate and correlate functional genomics data to in vivo pathophysioiogy of disease mechanisms. The ultimate goal of this project is to identify new genes and proteins that contribute to (specific steps in) the development of diabetic renal disease.